The most rapidly expanding age group of HIV-infected individuals are youth between the ages of 19 and 24 with more than 25% of new U.S. cases. Recreational marijuana use is the drug of choice by many youth living with HIV [YLWH]. Little is known about the effect of marijuana, which is regularly used in combination with tobacco products, on overall health. New treatment guidelines result in most YLWH initiating therapy before CD4 T cell decline. However, early treatment fails to reverse the long term inflammatory complications of HIV- mediated macrophage activation. There are no evidenced-based assessments of how the recreational use of marijuana impacts pro-inflammatory pathways in YLWH. The goals of the study are to define the potential health benefits and/or risks associated with self-administered marijuana. The significance of the study is accentuated by the increasing legalization of marijuana for recreation use. The long term goal is to discover evidence that provides the basis for understanding the complex and at times conflicting roles for marijuana in immune modulation. Two interconnected specific aims are designed: Aim 1. To identify inflammatory immune pathways perturbed by recreational marijuana with or without concomitant use of tobacco products by applying a deep sequencing approach to define global transcriptome of peripheral blood cells from HIV-infected virally suppressed youth. Aim 2. To develop biomarker profiles associated with pro- or anti-inflammatory pathways perturbed by marijuana and to discover biomarker profiles linked to neurocognitive impairment that are impacted by recreational marijuana and tobacco use by YLWH. Proposed study focus on YLWH who were enrolled in longitudinal studies in the Adolescent Trials Network Protocols as well as a prospectively enrolled population of YLWH recruited from the University of North Carolina. Longitudinal and cross sectional blood samples, clinical, demographic, behavioral, [including substance use and frequency], and neurocognitive data will be evaluated from YLWH treated before CD4 T cell decline. The participants reflect a key populations most impacted by HIV-infection, primarily minority men who have sex with men between the ages of 18 and 24 years. A comparative cohort of HIV-uninfected youth balanced for age, ethnicity, and gender is included. The investigators include an interdisciplinary team with considerable expertise in HIV infection, immunity, adolescent medicine, neurocognitive function, substance use, biostatistics, and bioinformatics. Results will define marijuana use consequences on molecular mechanisms of chronic macrophage activation in YLWH who do, or do not, engage in substance use. Proposed project aims are all high priority research areas in HIV, in particular its focus uses a systems biology approach to immune activation and inflammation in YLWH who use substances of abuse.